Fortimicin A

MOLECULAR FORMULA :

C17-H35-N5-O6.2H2-O4-S

MOLECULAR WEIGHT :

601.73

WISWESSER LINE NOTATION :

T6OTJ CZ FYZ1 BO- AL6TJ BZ CQ DO1 EN1&V1Z FQ &..H2.S-O4 2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>10 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

913 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1364 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

86 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 53,399,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1009 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 53,399,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

13600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

533 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

546 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,967,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

94 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 53,399,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

427 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - muscle weakness Behavioral - ataxia

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

214 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

750 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia Lungs, Thorax, or Respiration - other changes

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

654 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,19,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

611 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 53,399,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1500 mg/kg/30D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,4245,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1500 mg/kg/30D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4500 mg/kg/26W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - urine volume increased Blood - changes in erythrocyte (RBC) count

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),137,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

3 gm/kg/30D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),155,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

9 gm/kg/26W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),155,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

8391 mg/kg/91D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

REFERENCE :

DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 10,237,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1500 mg/kg/30D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in bladder weight Endocrine - changes in spleen weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,3905,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

6 gm/kg/30D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,3905,1986 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

1100 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,4274,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

550 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,4274,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

5170 mg/kg

SEX/DURATION :

female 22 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),167,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

275 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),167,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1210 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),167,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

21 gm/kg

SEX/DURATION :

male 8 week(s) pre-mating female 3 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 29(Suppl 2),167,1981